共查询到20条相似文献,搜索用时 46 毫秒
1.
Despina K. Laimou Maria Katsara Minos-Timotheos I. Matsoukas Vasso Apostolopoulos Anastassios N. Troganis Theodore V. Tselios 《Amino acids》2010,39(5):1147-1160
Leuprolide [dLeu6, NHEt10]GnRH, a potent gonadotropin-releasing hormone (GnRH) agonist, is used in a wide variety of hormone-related diseases like
cancer and endometriosis. In this report, the conformational behaviour of Leuprolide and its linear synthetic analogues, namely
[Tyr5(OMe), dLeu6, Aze9, NHEt10]GnRH (1) and [Tyr5(OMe), dLeu6, NHEt10]GnRH (2) have been studied in DMSO and H2O solutions by means of 2D nuclear magnetic resonance (NMR) experiments and detailed molecular dynamics (MD) simulations.
The aim was to identify the conformational requirements of GnRH analogues for agonistic activity. This approach is of value
as no crystallographic data are available for the GnRH receptor (G protein-coupled receptor, GPCR). The NOE data indicate
the existence of a β-turn type I in the 2–5 segments of Leuprolide and its linear analogues in the case of using DMSO-d6 as solvent, whereas a β-turn type II in the 3–6 segments is indicated using D2O as solvent. The final structures fulfil the conformational requirements that are known, in the literature, to play a significant
role in receptor recognition and activation. Finally, the linear analogues (1) and (2) are biologically active when tested against the human breast cancer cell line, MCF-7. 相似文献
2.
Local therapy with interleukin-2 (IL-2) and other cytokines may be a very effective way to treat cancer. This was the theme
of the First Symposium on Local Cytokine Therapy of Cancer: Interleukin-2, Interferons and Related Cytokines, in Hamburg,
29 April–1 May 1999. The abstracts are published in Anticancer Research 19: 1995–2016 (1999) [1]. Here we present a report.
Received: 28 October 1999 / Accepted: 2 December 1999 相似文献
3.
The association between polymorphism of DNA methyltransferases 3B and cancer risk has been widely studied recently, and no
consensus conclusion is available up to now. We perform a comprehensive search using the databases of Medline, ISI Web of
Knowledge and Embase. The odds ratio (OR) and its 95% confidence interval (95% CI) are used to investigate the strength of
the association. A total of 24 case–control studies with 15,647 individuals are included in this meta-analysis. For −149C > T
(17 studies, 5229 cases and 6910 controls), no evidence indicate that individuals carrying the variant genotypes (CC + CT),
relative to those carrying the wild homozygote TT genotype, have an increased risk of cancer (OR = 1.03; 95% CI = 0.84–1.26;
P = 0.76). Similarly, no cancer risk is found in the subgroup analyses. For −579G > T (11 studies, 3513 cases and 3714 controls),
significantly decreased risks of cancer are observed, and the ORs (95% CI) are 0.70 (0.56–0.87) for GT versus TT, 0.70 (0.57–0.85)
for GG + GT versus TT and 0.76 (0.63–0.93) for G-allele versus T-allele, respectively. Subgroup analyses stratified by ethnicity
and types of cancer are also performed, and results indicated that −579G > C polymorphism is associated with risk of cancer
in Asians [0.68 (0.53–0.87) for GT vs. TT] but not in Europeans [0.82 (0.63–1.07) for GT vs. TT]. We also observe that the
−579G is associated with decreased risk of colorectal cancer [0.49(0.38–0.62) for GT vs. TT]. More studies with larger sample
size were needed to provide more precise evidence. 相似文献
4.
This study aimed to perform a meta-analysis to assess the association of survivin −31 G/C promoter polymorphism and cancer
risk. Thirteen case–control studies identified through PubMed and published between 2007 and 2011 with a total of 3329 cancer
cases and 3979 controls were included in this meta-analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used
to investigate the strength of the association. Overall, the pooled analysis showed that survivin −31C allele was associated
with 1.27 fold increased risk of cancer compared with the −31G allele (95% CI = 1.091–1.479; random model). Subgroup analyses
based on type of cancer and ethnicity were also performed, and results indicated that survivin −31G/C polymorphism was not
associated with risk of gastric cancer [OR = 2.879; 95% CI = 0.553–15.004) for CC vs.GG] and esophageal cancer [OR = 1.352;
95% CI = 0.494–3.699) for CC vs.GG]. Stratification on the basis of ethnicity showed that the risk due to −31C allele was
significant only in Asian population [OR = 1.894; 95% CI = 1.206–2.974 for CC vs.GG]. The present meta-analysis suggests an
important role of survivin −31 G/C polymorphism with cancer risk especially in Asian population. However, further studies
with larger sample size are required to draw more comprehensive conclusions and provide more precise evidence in individual
cancers. 相似文献
5.
Rekowski Piotr Borowiec Agnieszka Drużyńska Joanna Kusiak Elżbieta 《International journal of peptide research and therapeutics》1998,5(5-6):417-420
Summary The solid-phase synthesis andin vitro assays on the glucose-induced insulin secretion from rat pancreatic islets of Langerhans with six new chimeric peptides were
performed. All the peptides were built up of the N-terminal galanin (GAL) fragment or its analogues, linked to the C-terminal
portion of substance P (SP) analogues or scyliorhinin I (SCY-I) analogues. Two strong antagonists of the inhibitory effect
of galanin on the glucose-induced insulin release were found: [cycloleucine4]GAL(1–13)-SP(5–11)-amide and GAL(1–13)-[L-norleucine10]SCY-I(3–10)-amide. 相似文献
6.
Y. Engelborghs 《European biophysics journal : EBJ》1998,27(5):437-445
The kinetic mechanisms of the binding to tubulin of colchicine and eight different analogues have been studied to elucidate
details of the recognition mechanism. All of the analogues follow a two step binding mechanism i.e. binding occurs via an
initial step with low affinity, followed by an isomerisation of the initial complex leading to the final high affinity state.
For several analogues the kinetic and thermodynamic data of both processes are compared here. For all the analogues the ΔG°1 of initial binding at 25 °C varies between –13.3 and –28.8 kJ ⋅ mol–1. For the second step ΔG°2 varies between –2.4 and –27 kJ ⋅ mol–1. These limited ranges of free energy change are, however, obtained by a great variety of enthalpy changes and compensatory
entropy changes. Comparison of the data for the first and second steps indicates that structural alterations of the drugs
always change the thermodynamic parameters of the two steps, and the changes in the first and the second steps are in opposite
directions. The fact that this range of experimental behaviour can be incorporated into a general mechanism encourages the
extension of these investigations to other colchicine analogues and related compounds with potential pharmaceutical applications.
Received: 9 January 1998 / Revised version: 2 March 1998 / Accepted: 7 March 1998 相似文献
7.
Barbara Biondi Dante Goldin Elisa Giannini Roberta Lattanzi Lucia Negri Pietro Melchiorri Luigi Ciocca Raniero Rocchi 《International journal of peptide research and therapeutics》2006,12(2):139-144
Syntheses are described of the nociceptin (1–13) amide [NC(1–13)-NH2] and of several analogues in which either one or both the phenylalanine residues (positions 1 and 4), the arginine residues (positions 8 and 12) and the alanine residues (positions 7 and 11) have been replaced by N-benzyl-glycine, N-(3-guanidino-propyl)-glycine and β-alanine, respectively. The preparation is also described of NC(1–13)-NH2 analogues in which either galactose or N-acetyl-galactosamine are β-O-glycosidically linked to Thr5 and/or to Ser10. Preliminary pharmacological experiments on mouse vas deferens preparations showed that Phe4, Thr5, Ala7 and Arg8 are crucial residues for OP4 receptor activation. Manipulation of Phe1 yielded peptides endowed with antagonist activity but [Nphe1] NC(1–13)-NH2 acted as an antagonist still possessing weak agonist activity. Introduction of the βAla residue either in position 7 or 11 of the [Nphe1] NC(1–13)-NH2 sequence, abolished any residual agonist activity and [Nphe1, βAla7] NC(1–13)-NH2 and [Nphe1, βAla11] NC(1–13)-NH2 acted as competitive antagonists only. Modification of both Ala7 and Ala11 abolished the antagonist activity of [Nphe1]NC(1–13)-NH2 probably by hindering receptor binding. Changes at positions 10 and 11 gave analogues still possessing agonist activity. [Ser(βGal)10] NC(1–13)-NH2 displayed an activity comparable with that of NC(1–13)-NH2, [Ser(βGalNAc)10] NC(1–13)-NH2 and [βAla11] NC(1–13)-NH2 were five and 10 times less active, respectively.The α-amino acid residues are of the l-configuration. Standard abbreviations for amino acid derivatives and peptides are according to the suggestions of the IUPAC-IUB Commission on Biochemical Nomeclature (1984), Eur. J. Biochem. 138, 9–37. Abbreviations listed in the guide published in (2003), J. Peptide Sci. 9, 1–8 are used without explanation. 相似文献
8.
The enzyme adenosine kinase (AK) plays a key role in the regulation of intracellular and extracellular concentration of adenosine
(Ado), which exhibits potent hormonal activity in cardiovascular, nervous and immune systems. In view of the pharmacological
effects of Ado, there is much interest in identifying inhibitors of AK, which can augment its tissue-protective effects. In
this study, we have screened 1040 compounds from a chemical library of putative kinase inhibitors for their effect on purified
human recombinant AK. These studies have identified 8 novel, non-nucleoside AK inhibitors. Four of these compounds (viz. 2-tert-butyl-4H-benzo[1,2,4]thiadiazine-3-thione
(2759–0749); N-(5,6-diphenyl-furo[2,3-d]pyrimidin-4-yl)-propionamide (3998–0118); 3-[5,6-Bis-(4-methoxy-phenyl)-furo[2,3-d]pyrimidin-4-ylamino]-propan-1-ol
(4072–2732); and 2-[2-(3,4-dihydroxy-phenyl)-5-phenyl-1H-imidazol-4-yl]-fluoren-9-one (8008–6198)), which inhibited human
AK in a concentration-dependent manner in a low micromolar range (IC50 = 0.38 ∼ 1.98 μM) were further studied. Kinetic and structural studies on these compounds provide evidence that inhibition
of AK by these compounds was competitive with respect to Ado and non-competitive for ATP. All of these compounds also inhibited
uptake of Ado and its metabolism in cultured mammalian cells at comparable concentrations indicating their efficient cellular
penetrability. These AK inhibitors, whose chemical structures differ significantly from all previously known inhibitors, provide
useful lead compounds for identification of more potent but less toxic AK inhibitors that may prove useful for therapeutic
purposes. 相似文献
9.
Peter R. Andreana Przemyslaw Kowal Adam J. Janczuk Peng George Wang 《Glycoconjugate journal》2003,20(2):107-118
Galactose oxidase (EC 1.1.3.9, GAO) was used to convert the C-6′ OH of Galβ(1 → 4)Glcβ–OBn (5) to the corresponding hydrated
aldehyde (7). Chemical modification, through dehydratative coupling and reductive amination, gave rise to a small library
of Galβ(1 → 4)Glcβ–OBn analogues (9a–f, 10, 11). UDP-[6-3H]Gal studies indicated that α1,3-galactosyltransferase recognized the C-6′ modified Galβ(1 → 4)Glcβ–OBn analogues (9a–f,
10, 11). Preparative scale reactions ensued, utilizing a single enzyme UDP-Gal conversion as well as a dual enzymatic system
(GalE and α1,3GalT), taking full advantage of the more economical UDP-Glc, giving rise to compounds 6, 15–22. Galα(1 → 3)Galβ(1
→ 4)Glcβ–OBn trisaccharide (6) was produced on a large scale (2 g) and subjected to the same chemoenzymatic modification as
stated above to produce C-6″ modified derivatives (23–30). An ELISA bioassay was performed utilizing human anti-αGal antibodies
to study the binding affinity of the derivatized epitopes (6, 15–30). Modifications made at the C-6′ position did not alter
the IgG antibody's ability to recognize the unnatural epitopes. Modifications made at the C-6″ position resulted in significant
or complete abrogation of recognition. The results indicate that the C-6′ OH of the αGal trisaccharide epitope is not mandatory
for antibody recognition. Published in 2004.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
10.
Yurixhi Maldonado–López Edelmira Linares–Mazari Robert Bye Guillermo Delgado Francisco J. Espinosa–García 《Economic botany》2008,62(2):161-170
Mexican Arnica Anti–Inflammatory Action: Plant Age Is Correlated with the Concentration of Anti–inflammatory Sesquiterpenes
in the Medicinal Plant
Heterotheca inuloides
Cass. (Asteraceae). Mexican árnica (Heterotheca inuloides Cass.) is a widely used anti–inflammatory medicinal plant in Mexican folk medicine. Although it has been suggested that plant
age, fertilization, and harvesting regime influence the concentration of secondary compounds affecting the therapeutic activity
of the plant, the effect of these variables on the concentration of the Mexican árnica anti–inflammatory compounds was not
known. We quantified anti–inflammatory sesquiterpenes (caryolan–1, 9β–diol, cadalen–15–oic acid, 7–hydroxycadalene, 4–hydroxy–2–isopropyl–4,
7–dimethyl–1[4H] naftalinone, 7–hydroxy–4αH–3, 4–dihydrocadalene, β–caryophyllene, and β–caryophyllene epoxide) in Mexican
árnica plants subjected to fertilization and successive harvests of flowering stems, conditions that mimic the cultivation
and harvesting for árnica in México. Fertilization and successive harvesting and their interaction had no significant effect
on the concentration of anti–inflammatory compounds. However, the concentrations of these compounds were 60% higher in flowering
stems from 15–month–old plants than in those from 4– or 8–month–old plants and was independent of the number of harvests and
fertilization regime applied. 相似文献
11.
Carlos Fernandez-Patron Christine Zouki Randy M. Whittal John S. D. Chan Sandra T. Davidge János G. Filep 《Biological procedures online》2002,4(1):38-48
Recent evidence indicates novel role for matrix metalloproteinases (MMPs), in particular gelatinase A (MMP-2), in the regulation
of vascular biology that are unrelated to their well-known proteolytic breakdown of matrix proteins. We have previously reported
that MMP-2 can modulate vascular reactivity by cleavage of the Gly32-Leu33 bound in big endothelin-1 (ET-1) yielding a novel
vasoactive peptide ET-1[1–32]. These studies were conducted to investigate whether gelatinolytic MMPs could affect neutrophil-endothelial
cell attachment. ET-1[1–32] produced by MMP-2 up-regulated CD11b/CD18 expression on human neutrophils, thereby promoted their
adhesion to cultured endothelial cells. ET-1[1–32] evoked release of gelatinase B (MMP-9), which in turn cleaved big ET-1
to yield ET-1[1–32], thus revealing a self-amplifying loop for ET-1[1–32] generation. ET-1[1–32] was rather resistant to cleavage
by neutrophil proteases and further metabolism of ET-1[1–32] was not a prerequisite for its biological actions on neutrophils.
The neutrophil responses to ET-1[1–32] were mediated via activation of ETA receptors through activation of the Ras/Raf-1/MEK/ERK
signaling pathway. These results suggest a novel role for gelatinase A and B in the regulation of neutrophil functions and
their interactions with endothelial cells. Here we describe the methods in detail as they relate to our previously published
work.
Published: October 28, 2002 相似文献
12.
Gibasiewicz K Ramesh VM Lin S Redding K Woodbury NW Webber AN 《Photosynthesis research》2007,92(1):55-63
Summary Femtosecond transient absorption spectroscopy was applied for a comparative study of excitation decay in several different
Photosystem I (PSI) core preparations from the green alga Chlamydomonas reinhardtii. For PSI cores with a fully interconnected network of chlorophylls, the excitation energy was equilibrated over a pool of
chlorophylls absorbing at ∼683 nm, independent of excitation wavelength [Gibasiewicz et al. J Phys Chem B 105:11498–11506,
2001; J Phys Chem B 106:6322–6330, 2002]. In preparations with impaired connectivity between chlorophylls, we have found that
the spectrum of chlorophylls connected to the reaction center (i.e., with ∼20 ps decay time) over which the excitation is equilibrated becomes excitation-wavelength-dependent. Excitation at
670 nm is finally equilibrated over chlorophylls absorbing at ∼675 nm, whereas excitation at 695 nm or 700 nm is equilibrated
over chlorophylls absorbing at ∼683 nm. This indicates that in the vicinity of the reaction center there are two spectrally
different and spatially separated pools of chlorophylls that are equally capable of effective excitation energy transfer to
the reaction center. We propose that they are related to the two groups of central PSI core chlorophylls lying on the opposite
sides of reaction center. 相似文献
13.
V. Gut V. Čeřovský M. Žertová E. Körblová P. Maloň H. Stocker E. Wünsch 《Amino acids》2001,21(3):255-263
Summary. The paper describes the synthesis of Asu6-octapeptide derivatives by condensing two alternative pentapeptide fragments with Asu-containing tripeptides. After partial
deprotection these linear peptides compounds are subject to cyclization experiments aimed to give the N-terminal [1–9] sequence
of deamino-dicarba-eel calcitonin. This is a key substance for the semi-synthesis of the respective analogues of eel calcitonin.
Received November 27, 2000 Accepted December 8, 2000 相似文献
14.
William J. Trickler Jatin Khurana Ankita A. Nagvekar Alekha K. Dash 《AAPS PharmSciTech》2010,11(1):392-401
The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures,
and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size,
and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular
internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2
and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 ± 28.6 nm, and 385.2 ± 16.1 nm, respectively with a surface charge of +21.94 ± 4.37
and +21.23 ± 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on
MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in
cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone.
The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared
with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic
compounds to potentially provide an effective treatment option in human pancreatic cancer. 相似文献
15.
Michael J. Seckl Enrique Rozengurt 《International journal of peptide research and therapeutics》1998,5(2-3):199-204
Summary Neuropeptides including bombesin, vasopressin and bradykinin are increasingly implicated in the control of cell proliferation.
There is now considerable evidence that the growth of certain common cancers including small cell lung cancer (SCLC) can be
stimulated by multiple neuropeptides which act in an autocrine/paracrine fashion. Consequently, the development of broad spectrum
neuropeptide, antagonists could be of therapeutic interest. Indeed, certain substance P (SP) analogues including (DArg1, DPhe5, DTrp7,9, Leu11) SP and (Arg6, DTrp7,9, MePhe8)SP (6–11) inhibit the actions of multiple neuropeptides and block the growth of SCLC cells in vitro and in vivo. Moreover,
one of these compounds is now in a phase I clinical study and so an understanding of the mechanism of action of these SP analogues
is both of fundamental as well as clinical interest. We have found that the SP analogues coordinately and reversibly inhibit
the downstream signals which emanate from neuropeptide receptors and competitively block the binding of neuropeptides to their
respective receptors. These and other results using novel SP analogues which are reviewed here, suggest that the SP analogues
act directly on the neuropeptide receptors to block neuropeptide action. 相似文献
16.
Frédéric Schmitt Mathieu Auzias Petr Štěpnička Yoshihisa Sei Kentaro Yamaguchi Georg Süss-Fink Bruno Therrien Lucienne Juillerat-Jeanneret 《Journal of biological inorganic chemistry》2009,14(5):693-701
Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(μ2-η2-O2CR)2L2] containing a Ru–Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands
in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1–3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence
and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma
cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head
and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence
of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying
an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive
system and not for normal cells; thus being promising new organometallic photosensitizers. 相似文献
17.
E. Walter Helbling M. Eugenia Farías M. Verónica Fernández Zenoff Virginia E. Villafañe 《Hydrobiologia》2006,559(1):123-134
In situ experiments were conducted at various depths in the water column to determine the effects of solar ultraviolet radiation
(UVR, 280–400 nm) on photosynthesis of natural phytoplankton assemblages from the subtropical Lake La Angostura (Argentina,
26°45′ S; 65°37° W, 1980 m asl.). Water samples were taken daily and incubated under three radiation treatments: (a) Samples
exposed to UVR + Photosynthetic Available Radiation (PAR) – PAB treatment (280–700 nm); (b) Samples exposed to ultraviolet-A
radiation (UV-A) + PAR – PA treatment (320–700 nm), and, (c) Samples exposed to PAR only – P treatment (400–700 nm). Additionally,
depth profiles were done to determine different physical (i.e., temperature and underwater radiation field) and biological
characteristics of the water column – photosynthetic pigments, UV-absorbing compounds, cell concentration, deoxyribonucleic
acid (DNA) and cyclobutane pyrimidine dimers (CPDs). The effects of UVR on natural phytoplankton assemblages were significant
only in the first 50 cm of the water column, causing a decrease in photosynthetic rates of 36 and 20% due to UV-A and ultraviolet-B
radiation (UV-B), respectively; below this depth, however, there were no significant differences between radiation treatments.
Concentration of CPDs per mega base of DNA in natural phytoplankton was low, <27 CPDs MB−1 between 0 and 4 m. Data on net DNA damage, together with that on mixing conditions of the water column, suggest that mixing
can favour phytoplankton by allowing cells to be transported to depths where active repair can take place. This mechanism
to reduce UVR-induced DNA damage would be of great advantage for these assemblages dominated by small cyanobacteria and chlorophytes
where UV-absorbing compounds that could act as sunscreens are virtually absent. 相似文献
18.
V. Ya. Smetanin 《Human physiology》2000,26(4):442-450
Physiological changes in the human organism are observed in different regimens of interval hypoxia. They are dependent on
several factors, including the strength of the hypoxic stimulus used (oxygen percentage of the air inhaled), time intervals
of some hypoxic positions, duration of the periods of normal respiration, and the total number of the recurrent hypoxic exposures
or the total duration of the hypoxic exposure during a day [1–4]. By changing the selected parameters of the hypoxic load,
it is possible to exert the necessary effect on particular physiological functions and to directly affect the main metabolic
reactions of the organism. This opens up new fields for the interval hypoxic exposures used as therapy for and preventive
treatment of different diseases [5–8], and for improving human health and increasing labor productivity [9–13]. The sports
training effect is caused by the combined effects resulting from changes in certain parameters of the physical load. When
using artificially induced interval hypoxia, it is possible to provide different regimens of physiological effects as is done
in sports training. That is the reason these regimens, proposed by the pioneers of this method, are called interval hypoxic
training [14–18]. The objective of this paper is to study the effect of different regimens of interval hypoxia on the cardiorespiratory
and hematological functions of athletes in order to use the data obtained to optimize interval hypoxic training. 相似文献
19.
Isolated adult mouse cardiomyocytes are an important tool in cardiovascular research, but are challenging to prepare. Because
the energy supply determines cell function and viability, we compared total creatine ([Cr]) and [ATP] in isolated cardiomyocytes
with the intact mouse heart. Isolated myocytes suffered severe losses of Cr (−70%) and ATP (−53%). Myocytes were not able
to replete [Cr] during a 5 h incubation period in medium supplemented with 1 mM Cr. In contrast, adding 20 mM Cr to the digestion
buffers was sufficient to maintain normal [Cr]. Supplementing buffers with 5 mM of inosine (Ino) and adenosine (Ado) to prevent
loss of cellular nucleosides partially protected against loss of ATP. To test whether maintaining [ATP] and [Cr] improves
contractile function, myocytes were challenged by varying pacing rate from 0.5 to 10 Hz and by adding isoproterenol (Iso)
at 5 and 10 Hz. All groups performed well up to 5 Hz, showing a positive cell shortening–frequency relationship; however,
only 16% of myocytes isolated under standard conditions were able to sustain pacing with Iso challenge at 10 Hz. In contrast,
30–50% of the myocytes with normal Cr levels were able to contract and maintain low diastolic [Ca2+]. Cell yield also improved in Cr and the Cr/Ino/Ado-treated groups (85–90% vs. 70–75% rod shaped in untreated myocytes).
These data suggest that viability and performance of isolated myocytes are improved when they are protected from the severe
loss of Cr and ATP during the isolation, making them an even better research tool. 相似文献
20.
Aikaterini A. Zompra Vassiliki Magafa Dimitra G. Chryssanthi Fotini N. Lamari Georgios A. Spyroulias Theodosia Maina Berthold A. Nock Nikos K. Karamanos Paul Cordopatis 《International journal of peptide research and therapeutics》2007,13(1-2):143-149
GnRH analogues have been extensively used in oncology to induce reversible chemical castration due to their hypophysiotropic
action. In addition to that, it has recently been shown that many malignant cells, such as breast cancer cells, locally produce
GnRH and express the GnRH receptor/s. In order to investigate the structure-activity relationships in both pituitary and extrapituitary
biological systems, we synthesized eight new GnRH analogues with modifications in the N-terminal part and/or in position 6
and studied their pituitary binding affinity (in αT3-1 cell membranes) and effect on breast cancer (MCF-7) cell proliferation.
2-Amino-4-pyrrolidinothieno[2,3-d]pyrimidine-6-carboxylic acid (ATPC) was incorporated instead of pGlu1-His2- and/or Gly6 was substituted by α-aminoisobutyric acid, D-Leu and D-Lys (alone or covalently linked to Gly, Ala, Sar, ATPC). Most GnRH
analogues lacked the carboxy-terminal Gly10-amide of GnRH and an ethylamide residue was added to Pro9, a modification common in many potent GnRH agonists, such as leuprolide ([D-Leu6, des-Gly10]-GnRH-NHEt. Results show differential impact of these modifications on the binding affinity to the GnRH receptor in mouse
pituitary cells and on the inhibition of human breast cancer cell proliferation. ATPC in the N-terminus resulted in analogues
with low binding affinity but high antiproliferative effect. Substitutions in position 6 always resulted in high binding affinities.
In particular, [D-Lys6(Gly), desGly10]-GnRH-NHEt and [D-Lys6(Sar), desGly10]-GnRH-NHEt have higher pituitary binding affinity than leuprolide, but only the latter had significant antiproliferative
effect on both MCF-7 and MDA-MB-231 cells. These results contribute to the on-going research for more potent GnRH analogues.
Abbreviations of common amino acids are in accordance with the recommendations of IUPAC-IUB Joint Commission on Biochemical
Nomenclature: Arch. Biochem. Biophys. 206, pp.v-xxii (1988), J. Biol. Chem. 264, 668–673 (1989) or J. Peptide Sci. 9, 1–8
(2003). 相似文献